The Molecules for life (the small ones) part 2

Now onto the organic and fatty acids!
Organic acids are very important due to their roles in complex chemical reaction, although not being very exciting chemicals themselves. If the cell is not supplied with them and with sugars, it soon is not able to sustain its protein and lipid organelles.
Some examples: (Using common names)
Acetic acid

Acetic Acid

Succinic acid

Fumaric acid

Citric acid

Pyruvic acid

Fatty acids are also vital for the structural role they have within the cell, specifically in cell membranes.They act as a barrier to polar substances in the membranes, as they are relatively long hydrocarbon chains with only a small acidic COOH group on the end. This makes them non-polar, and therefore hydrophobic, themselves, which is very useful to ensure that water levels inside and outside of the cell can be carefully controlled.
The acidic group is also important, as it allows the fatty acid to combine easily with other organic molecules, e.g. to make lipids!
Their long hydrocarbon chain parts can also be unsaturated (contain a carbon-carbon double bond):

  If they are unsaturated however it means that their can be two molecular configurations surrounding the double bond:

Top - cis
Bottom - trans

 This determines how straight the fatty acid is, as in the trans position the symmetry of the molecule keeps it straight, but in the cis position the chain becomes bent and changes direction. This then determines the fluidity of the fatty acids, which also plays an important role in controlling membrane stability.

Source: The Chemistry of Life by Steven Rose

The Molecules for Life (the small ones) part 1

The main essential molecules are phosphates, organic, fatty, and amino acids, sugars and purines and pyrimidines!
We'll start with the phosphate ion: PO4^3-

How it normally exists in the cell: Phosphoric acid, H3PO4

Phosphoric acid

Why it is important:
 Unlike other inorganic ions it combines very readily with other organic compounds because it has strong electronegativity, and so forms salts, e.g. potassium phosphate K3PO4, and esters, (mono-, di-, or triphosphate esters).

Triphosphate ester (where R is any organic alcohol)

 The phosphate ester is especially useful as it can convert a previously pretty much inert organic compound into a much more reactive one, with di- and triphosphate esters making them even more reactive than monophosphate ones. This is vital in particular for adenine triphosphate, or ATP, which I will go into later.

Source: The Chemistry of Life by Steven Rose

PTEN gene

Melanomas are a type of skin cancer. Although not quite as common as some, they can be very dangerous, due to their greater likelihood become malignant and spread than other cancers (thought to be because pigment cells are migratory cells already). They are also able to colonise most other areas of the body. All of which means they are extremely deadly.

Melanoma

Now scientists have discovered a set of genes, including the PTEN gene, which control how the melanoma cells shift rapidly between two shapes - one of the reasons why they can spread so easily. They can have rounded shapes, which they normally use to travel in the blood, or elongated shapes, which they use to travel through harder tissue, e.g. bone.
From studying fruit flies (whose cells have 5 different shapes as they grow during the flies' lifetime) it has been discovered experimentally, from switching off certain genes, which genes correspond to which shapes.
It has been found to be the same with melanoma cells - and specifically switching off the PTEN gene means that there are more elongated cells than rounded cells, and so can then more easily escape from the skin and advance to other areas. PTEN being deactivated is common in most cancers, for one in eight melanomas the gene isn't active.
Although this discovery at the moment is simply observational, hopefully it will lead to future options in helping treat and prevent melanomas.

Source: Genes help spread of shape-shifting skin cancer cells from the Conversation.

Homeostasis vs Homeodynamic

Recently in a book (The Chemistry of Life by Steven Rose) I was reading I came across an interesting point about the word 'homeostasis'. Homeostasis is defined as the tendency toward a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes, and is often used when studying life.
 Put simply, it means how an organism maintains itself as it is altered and changed by environmental factors.
For example, water levels in the body have to be carefully controlled, to ensure that no cells are damaged from osmosis. If too much water enters the cell it can cause lysis, or if too much water exits the cell it can lead to crenation, for red blood cells.

However the problem of using the word homeostasis in regards to living organisms is that organisms, both as a species and individuals, do not remain the same. As an individual they are born, they grow, the reproduce, they age and, eventually, they die. As a species they adapt, and evolve, over millions and millions of years.
 The book suggests that a more accurate word would instead be 'homeodynamic'. This would then describe the need for constancy as the organism changes, both in response to its own internal growth and also any environmental influences.

I do not expect that the word will actually change anytime soon, but I will probably start using the term instead for this blog.

(Sorry for the long delay in posts!!! I have been away for awhile - but I hope to get back to this blog now!)

Source: The Chemistry of Life by Steven Rose (I may use this source a lot too!)

How neurons grow

Cultured hippocampal neurons

How do neurons know exactly where they're supposed to go? How do they connect to the correct parts of the brain, and don't just wander aimlessly? Well, let's use the retina of tadpoles as an example, being rather unique as when they become frogs their vision changes from monocular to binocular.
An axon from each retina cell is grown toward the optic area of the brain - seemingly pulled along by a growth cone at its tip, which then determines the direction the axon grows. Unsurprisingly, this direction of growth appears to be affected mostly by chemicals which attract and repel the growth cone, directing it to where it needs to be. When it reaches the optic part, the axons from each eye cross over each other, such that the right half of the brain corresponds to the left eye, and the left half to the right eye.
But once the metamorphosis into frog-y-ness starts, the nerves have to change, relatively quickly. In order for the frog to be able to see with both eyes together, the right and left halves of each eyes' axons must end up together.
So new neurons are once again grown - but they end up going to different places. How they do this was discovered by investigations from Christine Holt and Shin-ichi Nakagawa. They found that ephrin B, a gene which opposes the growth cone, is activated. The reason then that only half of the growth cones are affected is because only half express the gene receptor for ephrin B - so half are repelled, and half simply grow regardless of the gene, meaning that the frog can now correctly interpret its binocular vision.
So ephrin B acts as a signal for axons - and you guessed it! There are others for other axons, however perhaps fewer than you might think. So far four main types have been found - ephrins,semaphorins, slits, and netrins (although netrins are slightly different as they usually attract neurons while the rest repel them.) And although there may not seem to be enough, it is likely that these are actually all that are required - as scientists are finding them in many parts of the brain, for many many different animals. This is a rather good example of how only a few genes/proteins, can work in different ways to create many dissimilar things, which on the surface appear so different but are actually remarkably similar.
The practically-exactly-the-same small things make deceptively different big things.


Source: Nature via Nurture by Matt Ridley

Gene therapy

As you almost certainly know there are genetic traits which are passed on to offspring - they can be relatively obvious, like hair colour, eye colour,  etc., or less obvious, e.g. cognitive ability or behaviour. (Often this is because it is also very much influenced by your environment as well - for example your family, friends, and early experiences.) However one major problem is that there are many genetic disorders which are also passed on. These can be very challenging, not only on account of the suffering caused for the individual, but also in that it can make things much more complicated if they want to have children themselves.

However, Italian researchers have now come up with a new method to help treat or reverse such diseases!

Gene therapy itself is rather simple in theory. The aim is to replace the dysfunctional gene with the correct version, which will hopefully lead to the correct proteins being made, and the possible reversal of the disorder.
Unfortunately, there are many problems with this: One very simple one being it is incredibly hard to identify which gene is faulty. Since, with a great many genetic diseases there are many different genes which are involved. Moreover, sometimes it's not even that any one gene is faulty, but because they've all come together in a certain way.

The current method for changing the DNA in each cell is by just using an altered virus to act as a vector for the new gene. The new method uses haematopoietic stem cells (HSCs) as well. This was initially prompted by research into treating three children with metachromatic leukodystrophy (MLD), which has a singular faulty gene as its cause, the ARSA gene. The gene encodes information used by lysosomes, a vesicle containing powerful hydrolytic enzymes, used for the digestion of unwanted material in cells. In MLD patients these don't work correctly in nerve cells, so they begin to slowly decline, leading to brain and spinal cord degeneration, and sensory deprivation.
However, the cells are incredibly difficult to insert a correct copy of the gene into, as they have, unsurprisingly, many biological defenses. To overcome these HSCs were used! (Cells normally found in bone marrow.) Benign viruses carrying a working copy of ARSA were then added to such cells taken from each person, and put back into the bloodstream to act as vectors.
These engineered cells corrected defective cells in the nervous system by supplying the normal version of ARSA. Because these were stem cells, they also reproduced to form new blood cells that themselves took on the same supportive roles, which helped fix the problem!

Hopefully many more such advances in gene therapy will mean that lots more genetic disorders will be able to be treated.

Source: Gene therapy using stem cells prevents inherited diseases: from the Conversation.

The ASPM gene!!!

One interesting fact I came across recently was about the ASPM gene. This gene can be found on chromosome 1, and it is rather large (10,434 letters long, divided into 28 paragraphs or 'exons'). But the most interesting fact about this gene is that between the 16th and 25th exons there is a single phrase of letters which is repeated over and over again. And it has been found that the number of times this pattern is repeated in the gene of an animal is linked proportionally to the number of neurons in its adult brain!
But it gets better - the arrangement usually starts with isoleucine and glutamine, respectively abbreviated to I and Q. This means that the number of 'IQ' repeats on the ASPM gene could correspond to the relative IQ of the species!
(Note: you are not expected to find this humorous yourself - but there may be a few nerds among you that do. I hope.)
But back to serious learning - the method by which this gene achieves this is it appears to determine the number of times neuronal stem cells in the brain are able to divide roughly two weeks after conception, which then controls how many neurons there will be. There will almost certainly be other factors that also play important parts of course, but I for one am rather excited about the prospect of there being (to simplify things probably too much) an 'IQ gene'.


Source: Nature via Nurture by Matt Ridley (I may end up using this source a lot!)